A Drug-drug Interaction Study to Evaluate the Effect of Rifampicin and Febuxostat on the Pharmacokinetics of Methotrexate in Healthy Subjects

To investigate the effect of rifampicin and febuxostat on pharmacokinetics of methotrexate in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: Methotrexate Sodium; Drug: Rifampicin Sodium; Drug: Febuxostat Tablets

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age between 19 to 50, healthy male subjects (at screening)
• Body weight between 50.0 kg - 90.0 kg, BMI between 18.0 - 30.0 kg/m2
• Subject who totally understand the progress of this clinical trials, make decision by his free will, and signed a consent form to follow the progress

Exclusion Criteria:

• Subject who has a past or present history of any diseases (eg. liver, kidney, neurology, immunology, pulmonary, endocrine, hematology, oncology, cardiology, mental disorder)
• Subject who had GI tract disease (Crohn's disease, ulcer, acute or chronic pancreatitis) or surgery (appendectomy, hernioplasty are excluded)
• Serum AST(SGOT), ALT(SGPT), total bilirubin >1.5 times upper limit of normal range, MDRD eGFR < 60mL/min/1.73m2, WBC count < 3,500 /uL, SBP < 90 mmHg or > 150 mmHg, DBP < 50 mmHg or >100 mmHg
• Subject who had galactose intolerance, Lapplactase deficiency or glucose-galactose malabsorption
• Subject who had received drugs inhibiting or inducing metabolic enzymes/transporters such as barbiturates, statins, digoxin in 3 months
• Subject who had taken St.John's wort and food including grapefruit in 2 weeks
• Smoking in 3 months
• Subject who had whole blood donation in 2 months, or component blood donation in 1 month or transfusion in 1 month currently

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Methotrexate	Drug: Methotrexate Sodium; Methotrexate oral administration alone
EXPERIMENTAL: Methotrexate + Rifampicin	Drug: Methotrexate Sodium; Methotrexate oral administration alone; Drug: Rifampicin Sodium; Co-administration of methotrexate and rifampicin
EXPERIMENTAL: Methotrexate + Febuxostat	Drug: Methotrexate Sodium; Methotrexate oral administration alone; Drug: Febuxostat Tablets; Co-administration of methotrexate and febuxostat
EXPERIMENTAL: Methotrexate + Rifampicin + Febuxostat	Drug: Methotrexate Sodium; Methotrexate oral administration alone; Drug: Rifampicin Sodium; Co-administration of methotrexate and rifampicin; Drug: Febuxostat Tablets; Co-administration of methotrexate and febuxostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Cmax of methotrexate	Compare the maximum concentration (Cmax), area under the plasma concentration-time curve to last measurable time point (AUClast) and area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)
Compare AUClast of methotrexate	Compare the area under the plasma concentration-time curve to from 0 to last measurable time point (AUClast) of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)
Compare AUCinf of methotrexate	Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Cmax of 7-hydroxy methotrexate	Compare the maximum concentration (Cmax) of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)
Compare AUClast of 7-hydroxy methotrexate	Compare area under the plasma concentration-time curve to last measurable time point (AUClast) of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)
Compare AUCinf of 7-hydroxy methotrexate	Compare area under the plasma concentration-time curve from 0 hours to infinite time (AUCinf) of 7-hydroxy methotrexate	pre-dose (0h), 0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24 h post-dose (Period 1, 2, 3, 4 Day 1)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 20, 2021
• Primary Completion (ACTUAL): May 3, 2022
• Study Completion (ACTUAL): May 9, 2022

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (ACTUAL): October 12, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Reproductive Control Agents; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Gout Suppressants; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Methotrexate; Rifampin; Febuxostat
• Other Study ID Numbers: MRFI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No